A novel LIM protein Cal promotes cardiac differentiation by association with CSX/NKX2-5.
A novel LIM protein Cal promotes cardiac differentiation by association with CSX/NKX2-5.
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DOI：
10.1083/jcb.200309159
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发表时间：
2004-02-02
期刊：
影响因子：
--
通讯作者：
Komuro I
中科院分区：
文献类型：
--
作者：
Akazawa H;Kudoh S;Mochizuki N;Takekoshi N;Takano H;Nagai T;Komuro I
心脏同源盒转录因子CSX/NKX2-5在脊椎动物心脏发育中起重要作用。通过酵母双杂交筛选，我们发现了一个新的含有LIM结构域的蛋白，命名为CSX相关LIM蛋白（Cal），它与CSX/NKX2-5相互作用。CSX/NKX2-5与Cal在体内和体外均存在关联，Cal的LIM结构域和CSX/NKX2-5的同源结构域是相互结合的必要条件。Cal本身具有转录促进活性，同时转染Cal可增强CSX/ nkx2 -5诱导的房钠肽基因启动子的激活。Cal含有一个功能性核输出信号，并在钙的作用下从细胞质进入细胞核。P19CL6细胞核中Cal的积累促进心肌细胞分化，同时CSX/NKX2-5靶基因表达水平升高。这些结果表明，一种新的LIM蛋白Cal通过其细胞内动态穿梭和与CSX/NKX2-5的关联诱导心肌细胞分化。
The cardiac homeobox transcription factor CSX/NKX2-5 plays an important role in vertebrate heart development. Using a yeast two-hybrid screening, we identified a novel LIM domain–containing protein, named CSX-associated LIM protein (Cal), that interacts with CSX/NKX2-5. CSX/NKX2-5 and Cal associate with each other both in vivo and in vitro, and the LIM domains of Cal and the homeodomain of CSX/NKX2-5 were necessary for mutual binding. Cal itself possessed the transcription-promoting activity, and cotransfection of Cal enhanced CSX/NKX2-5–induced activation of atrial natriuretic peptide gene promoter. Cal contained a functional nuclear export signal and shuttled from the cytoplasm into the nucleus in response to calcium. Accumulation of Cal in the nucleus of P19CL6 cells promoted myocardial cell differentiation accompanied by increased expression levels of the target genes of CSX/NKX2-5. These results suggest that a novel LIM protein Cal induces cardiomyocyte differentiation through its dynamic intracellular shuttling and association with CSX/NKX2-5.
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